Fig. 3: Fab DH63-A02 induces the catalytically active conformation of TG3.

a, b Previously solved crystal structures of proteolytically cleaved TG3 without bound substrate (a, PDB ID: 8OXW) or with a substrate-mimicking irreversible inhibitor (Z-DON, yellow stick) attached to the active site Cys (b, PDB ID: 8OXX). The structures were solved with bound anti-TG3 Fab DH63-B02, but the Fab is omitted in these representations. Color coding: N-terminal domain, dark blue; catalytic core domain, light blue; C1 domain, green; C2 domain, yellow; and calcium ions, green spheres. A β-sheet that is repositioned upon binding of substrate and departure of C1C2 is highlighted in magenta in (b). c, d Crystal structures of cleaved TG3 in complex with anti-TG3 Fab DH63-A02 (heavy chain, dark gray; and light chain, light gray). The structures were solved without inhibitor (c, PDB ID: 8RMX) or with Z-DON bound in the active site (d, PDB ID: 8RMY). e Closeup of paratope-epitope interactions between Fab DH63-A02 and TG3 with bound Z-DON (PDB ID: 8RMY). Direct H-bonds are depicted with red broken lines. Color coding for Fab CDR loops: CDR-H1, dark blue; CDR-L1, cyan; CDR-H2, dark green; CDR-L2, light green; CDR-H3, brown; and CDR-L3, orange.